2B4J

Structural basis for the recognition between HIV-1 integrase and LEDGF/p75

Summary for 2B4J

• Entry DOI: 10.2210/pdb2b4j/pdb
• Related: 1ITG 1K6Y 1z9e
• Descriptor: Integrase (IN), PC4 and SFRS1 interacting protein, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: hiv, integration, transcription, viral protein, recombination
• Biological source: Human immunodeficiency virus 1; More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P12497; Nucleus : O75475
• Total number of polymer chains: 4
• Total formula weight: 59524.24

Authors

Cherepanov, P.,Ambrosio, A.L.,Rahman, S.,Ellenberger, T.,Engelman, A. (deposition date: 2005-09-24, release date: 2005-10-25, Last modification date: 2023-08-23)

Primary citation

Cherepanov, P.,Ambrosio, A.L.,Rahman, S.,Ellenberger, T.,Engelman, A.
Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75
Proc.Natl.Acad.Sci.Usa, 102:17308-17313, 2005

PubMed Abstract: Integrase (IN) is an essential retroviral enzyme, and human transcriptional coactivator p75, which is also referred to as lens epithelium-derived growth factor (LEDGF), is the dominant cellular binding partner of HIV-1 IN. Here, we report the crystal structure of the dimeric catalytic core domain of HIV-1 IN complexed to the IN-binding domain of LEDGF. Previously identified LEDGF hotspot residues anchor the protein to both monomers at the IN dimer interface. The principal structural features of IN that are recognized by the host factor are the backbone conformation of residues 168-171 from one monomer and a hydrophobic patch that is primarily comprised of alpha-helices 1 and 3 of the second IN monomer. Inspection of diverse retroviral primary and secondary sequence elements helps to explain the apparent lentiviral tropism of the LEDGF-IN interaction. Because the lethal phenotypes of HIV-1 mutant viruses unable to interact with LEDGF indicate that IN function is highly sensitive to perturbations of the structure around the LEDGF-binding site, we propose that small molecule inhibitors of the protein-protein interaction might similarly disrupt HIV-1 replication.

PubMed: 16260736
DOI: 10.1073/pnas.0506924102

Experimental method

X-RAY DIFFRACTION (2.02 Å)